Non-viral gene delivery is an attractive alternative to viral delivery systems in that there have been relatively few reports of adverse effects associated with administration of non-viral delivery vehicles for DNA. Unfortunately, non-viral delivery systems (specifically cationic liposomes) have been hampered by inefficient gene delivery and inactivation by serum proteins upon intravenous administration. Preliminary data has shown that much of the low level expression can be attributed to the inefficient packaging of plasmid DNA within the delivery vehicle. Condensation of DNA with the cationic protein, protamine sulfate mimics the packaging of genetic material in mammals and produces a delivery system resembling an artificial sperm. This efficient condensation of DNA has been shown to result in an increase in the delivery of plasmid DNA 50-fold and provides protection from degradation by enzymes and nucleases. The ultimate goal of this research is to identify several condensation agents which will effectively package and protect DNA, allowing it to be incorporated into a cationic liposomal delivery system such that it may be safely and efficiently administered via a systemic route of injection. It is thought that this condensation process will impart stability and increased transgene activity necessary to overcome the inefficiencies of conventional non-viral gene delivery systems. PROPOSED COMMERCIAL APPLICATIONS: The research project proposed here will generate a greatly improved nonviral, liposomal gene delivery system which will be ubiquitously applicable to deliver genes, gene fragments, and oligonucleotides by various routes of administration including the parenteral and inhalatory route. It will, therefore, be applicable for gene therapy protocols of pulmonary diseases, metabolic diseases, cancer, and other diseases for which no therapeutic regimens are currently available.